Rheumatoid arthritis (RA) is a serious, chronic autoimmune disease that afflicts about 1% of the world's population. Women are affected three times more often than men. RA primarily attacks the joints, where an inflammatory synovitis frequently destroys articular cartilage and causes ankylosis. RA may involve other tissues in diffuse inflammation including lungs, pericardium, pleura, and sclera. RA is both crippling and painful, and frequently leads to substantial loss of mobility and overall function.
Diagnosis of RA is typically based initially on clinical signs and symptoms, but because the clinical indicators of RA are shared with a number of other common diseases and conditions, the clinical evaluation is usually supplemented by X-rays, and by blood tests for known markers, such as rheumatoid factor (RF). Thus, when RA is suspected from observation of clinical signs and symptoms, blood tests such as those testing for the presence of RF are typically used to help confirm a diagnosis. Known markers however do not necessarily detect RA with a very high level of sensitivity to RA and specificity for RA. For example, particularly during the earliest stages of RA in the first year, about 15-20% of patients do not seroconvert to RF and therefore an RF test on such a patient during this time will produce a false negative result. Moreover, RF is not 100% specific to RA, being present in about 10% of the healthy population and also in individuals with other inflammatory diseases or conditions, especially Sjögren's syndrome but also chronic hepatitis, any chronic viral infection, leukemia, dermatomyositis, infectious mononucleosis, systemic sclerosis and systemic lupus erythematosus. RF tests on such individuals will produce a significant number of false positive results. Serological markers of RA also include anti-citrullinated protein antibodies (ACPAs), as tested in the anti-CCP (cyclic citrullinated peptide) test and the anti-MCV (antibodies against mutated citrullinated Vimentin) assay, which also produce significant numbers of false positive and/or false positive results with respect to RA. Markers of RA with improved sensitivity to and specificity for RA are needed so that positive diagnoses of RA can be confirmed as early as possible in the course of the disease.